Considerations for Mesenchymal Stem Cell-Derived Small Extracellular Vesicle-Based Clinical Treatment of Spinal Cord Injury.

A large body of animal studies across multiple laboratories has found that a subset of small extracellular vesicles (sEVs) derived from mesenchymal stromal cells (MSC-sEVs) referred to as exosomes can improve functional recovery after spinal cord injury (SCI). Sufficient pre-clinical data have been accumulated to consider how MSC-sEVs might be used clinically for the treatment of SCI. This review discusses: (1) the SCI patient population which may benefit from MSC-sEVs treatments, (2) potential sources of MSCs for production of clinically useful MSC-sEVs, (3) dosaging of MSC-sEVs required for therapeutic efficacy, (4) timing and method of delivery of the sEVs, (5) cell targets of MSC-sEVs and their mechanism of action, (6) possible protocols for producing clinically useful quantities of MSC-sEVs, and (7) the criteria for evaluating an MSC-sEVs treatment product. We conclude with some thoughts about potential protocols for clinical trials of MSC-sEVs treatment for SCI.